DESCRIPTION (provided by investigator): Over 100 million women worldwide use some form of hormonal contraception (HC). Animal studies suggest that effects of sex hormones on immune responses are dependent on the duration of exposure. Human studies have rarely focused on this issue. Our overall hypothesis for this application is that the duration of HC use is a critical independent factor that contributes to the effects of HC on mucosal immune responses and the vaginal microbiota. The aims of this application are: 1. To establish a prospective cohort of women initiating HC and follow these women for two years. 2. To determine the short-term and longer-term impact of HC use on the structure of the vaginal microbial communities. 3. To define the impact of short term and longer-term HC use on pro-and anti-inflammatory cytokine and chemokine responses in the vagina, ectocervix, and endocervix. The longer-term goal is to establish a specimen repository from this cohort that would allow us to further define changes in mucosal and systemic immune responses. This application is a collaboration between Johns Hopkins University School of Medicine, Johns Hopkins Bloomberg School of Public Health, and the University of Maryland Institute for Genome Sciences. The team assembled for this study encompasses the multidisciplinary expertise in metagenomics, statistics, immunology, epidemiology, infectious diseases and gynecology necessary to exploit the data that will be generated. There is no doubt that HC play an important role in maintaining health, as well as economic, and political stability. As such, their continued use is vital and incontrovertible. Understanding how the short-term and long-term use of exogenous sex steroids impacts immune responses and the lower genital environment is critical to ensure that these agents are used in a way that maximizes safety and efficacy. The information generated from this research program should help drive the development of diagnostic tools and identify new targets to improve women's health. PUBLIC HEALTH RELEVANCE: Over 100 million women worldwide use hormonal contraceptives (HC). Our overall hypothesis for this application is that the duration of HC use is a critical independent factor that contributes to the effects of HC on mucosal immune responses and the vaginal microbiota. Our goal is to establish a cohort of women initiating HC, and to follow these women over 2 years to define how the duration of HC use impacts measures of mucosal immune function and the composition of the vaginal microbial communities.